In this file photo released by an official website of the Iranian supreme leader's office, Iran's supreme leader, Ayatollah Ali Khamenei, waves to worshipers, in front of a portrait of the late revolutionary founder Ayatollah Khomeini, before he delivers his Friday prayers sermon at the Tehran University campus last week.

But the words of Ayatollah Ali Khamenei – who has the final say on all strategic decisions in Iran, as official holder there of the title "God's deputy on earth" – appear to have scuppered chances of an immediate direct dialogue with the US.

"You [Americans] are pointing the gun at Iran and say either negotiate or we will shoot. The Iranian nation will not be frightened by the threats,"Mr. Khamenei told Air Force commanders in a speech today.

"Some naive people like the idea of negotiating with America [but] negotiations will not solve the problems," Khamenei said in the remarks, which were posted on his website. "If some people want American rule to be established again in Iran, the nation will rise up to face them."

US Vice President Joe Biden said Feb. 2 that Washington was ready for one-on-one talks "when the Iranian leadership, supreme leader, is serious." And in recent days, both President Mahmoud Ahmadinejad and Iran's foreign minister issued cautious, but explicit and positive, signals about possible direct contact with the US.

Foreign Minister Ali Akbar Salehi said there would be "positive consideration" of Mr. Biden's words, and that there was "no red line for bilateral negotiations" if the US was sincere.

Turning the screw

But yesterday the US tightened sanctions against Iran, forcing Iranian oil importers into barter arrangements to further restrict cash flow into the country. The sanctions are the latest in a host of measures by the US and the European Union that have crippled Iran's economy by choking its oil exports, central bank, and most financial transactions.

The moves taken yesterday were described by a senior Obama administration official as "a significant turning of the screw" that will “significantly increase the economic pressure on Iran.”

"Does imposing, in your own words, crippling sanctions show goodwill or hostility?" Khamenei asked today. "Iran will not accept to negotiate with he who threatens us with pressure. The offer of talks is meaningful when the other side shows goodwill."

Khamenei has nevertheless authorized Iran's talks with the six world powers, and said today, via Twitter, that "having relationships and negotiating with countries who had no deceit against us, is in our national interest."

The stated purpose of the raft of US and EU sanctions, along with four sets imposed by the United Nations Security Council since 2006 to hinder Iran's nuclear and missile programs, is to pressure Iran into agreeing to negotiated limits on its nuclear program so it can never build a bomb.

Iran says its nuclear program is peaceful and rejects nuclear weapons as un-Islamic. Khamenei has declared in the past that Iran would demonstrate that nuclear arms were not a prerequisite to being a global power. But Iran has been at loggerheads with inspectors of the UN nuclear watchdog agency regarding access and about possible past weapons-related work.

Diplomatic efforts to resolve the Iran nuclear standoff are taking place in the context of an ever-increasing economic war, with sanctions at their center.

There is also a covert war being waged against Tehran that has, in recent years, been marked by the assassination of several Iranian scientists and multiple acts of sabotage, including targeted computer viruses.

Iranian officials blame the US and Israel for this covert war. And Khamenei has often referred to it – along with sanctions – when accusing the US of trying to force regime change, rather than just a resolution to the nuclear issue.

Iran to US: You first

Khamenei raised questions about US sincerity soon after President Obama was inaugurated in 2009. In an initial overture, Mr. Obama said, "If countries like Iran are willing to unclench their fist, they will find an extended hand from us." Soon thereafter, Obama addressed the Iranian people and called for a "new beginning."

Khamenei reacted by saying that Obama had "insulted Iran." About the proffered hand of friendship, he said: "What kind of hand? If it is an iron hand covered with a velvet glove, then it will not make any good sense..."

Yet Khamenei also offered one thread of hope to the US. He said: "You change, and we will also change our behavior, too."

Since 2009, however, the violent aftermath of presidential elections in Iran that year made improvements untenable for both sides.

The covert war against Iran has also been stepped up, such that a regular theme in Khamenei's speeches has been the "iron fist" that he claims the US offered to the Islamic Republic, along with "lies" and insincere efforts to find common ground.

It is not clear what effect the rejection of bilateral US-Iran discussions will have on the next round of nuclear talks.

Analysts suggest that Washington hoped to bypass the rigid framework of the so-called P5+1 group (the US, Russia, China, Britain, France, and Germany), which handles the nuclear talks, in order to offer Iran an enhanced deal that would include permitting a level of uranium enrichment in Iran, and recognition of its "right" to enrich – both bottom-line demands by Iran.

Both Britain and France, especially, are seen to be unwilling to accept those steps in the P5+1 framework. Yet in three rounds of previous talks last spring and summer, all P5+1 players looked to Washington to shape the final, acceptable result.

The current P5+1 offer has been rejected by Iran. It requires Iran to first take several key steps to rein in its nuclear program, with no reciprocal guarantee that sanction relief will follow.

British Foreign Secretary William Hague said on Feb. 5 that there would be an “updated and credible offer for Iran” in Kazakhstan, and that the “need to make progress is increasingly urgent.”